Abstract: ob＜x＞jective To develop a green, simple and efficient method to construct pyrimidine-2-ketone skeleton molecules which could provide a material basis for the study of antitumor activity of these molecules. Methods Using 7-fluoroindoline -2,3-dione, urea and 4,4,4-trifluoro-1-(thiophene-2-yl) butane- 1,3-dione as substrates and p-methylbenzenesulfonic acid as the catalyst, the target compound was synthesized via Biginelli reaction in a multi-component one pot method without solvent. The crystal structure was verified by 1H NMR, 13C NMR, IR , HRMS and X-ray diffraction method. Results The target compound, 7’-fluoro-6-hydroxy-5 -(thiophene-2-carbonyl)-6-(trifluoroomethyl)spiro1,3diazinane-4,3’-indole-2,2’(1’ H)-dione was obtained in 82% isolated yield under solvent free conditions via one pot Biginelli reaction. The structure of the product was characterized by NMR, IR and HRMS, and further confirmed by X-ray diffraction. According to X-ray diffraction, the crystal structure belonged to the orthorhombic system , and the space group was P21/n．In addition, the direct method was used to analyze the crystal structure, and the atomic parameters corrected by the full matrix least square method showed that the final deviation factor was R = 0.3967，wR2 = 0.8133. Conclusions Pyrimidine-2-one skeleton molecule was successfully constructed via a multi-component Biginelli reaction under solvent-free conditions. The method is green and environment-friendly and the pure product can be obtained only by recrystallization.